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Similarities in genetic mental retardation and neuroteratogenic syndromes
1Department of Psychology, University of Massachusetts/Boston 02125, USA.
Insights
Neurobehavioral teratogenesis reveals shared developmental abnormalities from genetic factors or teratogen exposure. Understanding retinoid disruption of gene expression offers insights into birth defects and intellectual disability.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Neurobehavioral teratogenesis links genetic abnormalities and teratogenic exposures.
- Abnormal development shares common manifestations regardless of cause.
- Isotretinoin (Accutane) and genetic syndromes provide models for studying developmental disruptions.
Purpose of the Study:
- To compare neuropathological and neuropsychological characteristics of isotretinoin exposure and mental retardation syndromes.
- To explore mechanisms of retinoid teratogenesis and homeobox gene disruption.
- To propose a common basis for genetic syndromes and teratogenic effects.
Main Methods:
- Comparative analysis of neurodevelopmental outcomes.
- Examination of retinoid effects on embryogenesis and gene expression.
- Review of homeobox gene function in development.
Main Results:
- Commonalities identified between isotretinoin-induced and genetic developmental abnormalities.
- Disruption of homeobox gene expression proposed as a unifying mechanism.
- Dose-response and vulnerability factors influence developmental outcomes.
Conclusions:
- Shared pathways exist in neurobehavioral teratogenesis.
- Homeobox gene dysregulation is a potential common mechanism for craniofacial and hindbrain abnormalities.
- Variability in developmental abnormalities can be explained by dose-response and vulnerability factors.
Abstract:
Principles and mechanisms of neurobehavioral teratogenesis are used to show commonalities between manifestations of abnormal development consequent to genetic abnormality or teratogenic exposure. A comparison and contrast of both the neuropathological and neuropsychological characteristics of children with early embryonic exposure to isotretinoin (Accutane) or with selected mental retardation syndromes is presented. Putative mechanisms of retinoid teratogenesis through the disruption of normal retinoid-triggered embryogenesis and the alteration of homeobox gene expression are discussed. Interference with homeobox gene expression as an avenue to the perturbation of early developmental processes and the production of hindbrain and craniofacial abnormalities is then proposed as a common basis for the translation and expression of several genetic mental retardation syndromes. Finally, dose-response effects and other modulators of vulnerability to abnormal development are used to provide a conceptual framework for the understanding of variability in the expression of genetically caused abnormalities.